Identification of significant pathways in gastric cancer based on protein-protein interaction networks and cluster analysis

Abstract

Gastric cancer is one of the most common and lethal cancers worldwide. However, despite its clinical importance, the regulatory mechanisms involved in the aggressiveness of this cancer are still poorly understood. A better understanding of the biology, genetics and molecular mechanisms of gastric cancer would be useful in developing novel targeted approaches for treating this disease. In this study we used protein-protein interaction networks and cluster analysis to comprehensively investigate the cellular pathways involved in gastric cancer. A primary immunodeficiency pathway, focal adhesion, ECM-receptor interactions and the metabolism of xenobiotics by cytochrome P450 were identified as four important pathways associated with the progression of gastric cancer. The genes in these pathways, e.g., ZAP70, IGLL1, CD79A, COL6A3, COL3A1, COL1A1, CYP2C18 and CYP2C9, may be considered as potential therapeutic targets for gastric cancer.

Keywords: graph clustering; pathway crosstalk; protein-protein interaction network.

Figure 1

Clustering of correlated modules in gastric cancer (threshold r ≥ 0.75). The circles indicate clusters and the red lines (edges) indicate crosstalk (shared genes) between clusters.

Figure 2

Analysis of pathway crosstalk based on protein-protein interaction networks. The yellow circles indicate the pathways and the gray lines (edges) indicate the links between any two pathways.